DCAF7 regulates hematopoietic stem cell function and differentiation through polycomb repressive complex 1 modulation
Abstract
DCAF7 is one of the few DCAFs expressed in hematopoietic stem cells (HSCs). Using a conditional knockout mouse model, we discovered that the absence of DCAF7 leads to accumulation of differentiating progenitors in the bone marrow, and impairs self-renewal capacity of HSCs upon transplantation. Furthermore, loss of Dcaf7 accelerates the differentiation of HSCs into the myeloid lineage. At the molecular level, DCAF7 interacts with components of the polycomb repressive complex 1 (PRC1) and promotes their assembly into large macromolecular complexes. Chromatin profiling revealed that loss of DCAF7 leads to increased localization of RING1B at transcriptionally active genomic loci. This increased binding was observed at genes involved in myeloid differentiation and was associated with increased mRNA expression. Lastly, inhibition of KDM2/7 proteins rescues the defective growth of Dcaf7 null HSCs in vitro. Together, these data reveal that DCAF7 is a novel regulator of the PRC1 complex and epigenetic enzymes that control HSC differentiation.
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BibTeX
@article{melocardenas2026dcaf7,
title = {{DCAF7 regulates hematopoietic stem cell function and differentiation through polycomb repressive complex 1 modulation}},
author = {Johanna Melo-Cardenas and Lavanya Bezavada and Te Ling and Trent Hall and Amber Broadhurst and Anitria Cotton and Jeremy Chase Crawford and Amanda Nourse and Vishwajeeth Pagala and Kiran Kodali and Mollie S. Hutton and Shondra M. Pruett-Miller and Qiong Zhang and Wojciech Rosikiewicz and Hongjian Jin and Dirk Loeffler and John D. Crispino},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78299-x},
url = {https://www.nature.com/articles/s41467-026-78299-x},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - DCAF7 regulates hematopoietic stem cell function and differentiation through polycomb repressive complex 1 modulation
AU - Johanna Melo-Cardenas
AU - Lavanya Bezavada
AU - Te Ling
AU - Trent Hall
AU - Amber Broadhurst
AU - Anitria Cotton
AU - Jeremy Chase Crawford
AU - Amanda Nourse
AU - Vishwajeeth Pagala
AU - Kiran Kodali
AU - Mollie S. Hutton
AU - Shondra M. Pruett-Miller
AU - Qiong Zhang
AU - Wojciech Rosikiewicz
AU - Hongjian Jin
AU - Dirk Loeffler
AU - John D. Crispino
PY - 2026
DA - 2026/10/03
JO - Nature Communications
DO - 10.1038/s41467-026-78299-x
UR - https://www.nature.com/articles/s41467-026-78299-x
AB - DCAF7 is one of the few DCAFs expressed in hematopoietic stem cells (HSCs). Using a conditional knockout mouse model, we discovered that the absence of DCAF7 leads to accumulation of differentiating progenitors in the bone marrow, and impairs self-renewal capacity of HSCs upon transplantation. Furthermore, loss of Dcaf7 accelerates the differentiation of HSCs into the myeloid lineage. At the molecular level, DCAF7 interacts with components of the polycomb repressive complex 1 (PRC1) and promotes their assembly into large macromolecular complexes. Chromatin profiling revealed that loss of DCAF7 leads to increased localization of RING1B at transcriptionally active genomic loci. This increased binding was observed at genes involved in myeloid differentiation and was associated with increased mRNA expression. Lastly, inhibition of KDM2/7 proteins rescues the defective growth of Dcaf7 null HSCs in vitro. Together, these data reveal that DCAF7 is a novel regulator of the PRC1 complex and epigenetic enzymes that control HSC differentiation.
SN - 2041-1723
ER -